December 12, 2012

A few days ago I suggested that Dr. Daniel MacArthur might have South Asian ancestry. Now, when confronted with surprise the best option is to stick with your prior assumption, unless that surprise is powerful enough for you to “update” your model. After a few days of further analysis I will update: I do think Dan MacArthur has South Asian ancestry. Dienekes dug further, and noticed that there are hallmarks of “Ancestral South Indian” ancestry along the first 2/3 or so of chromosome 10. Now, you do have to remember that this genomic region is only half South Asian. The other half is European.

But in any case, one question that some people brought up: perhaps MacArthur has Romani heritage? I’m skeptical of this partly because:

1) there weren’t that many Romani in Britain in the 19th century

2) The British Romani are already very highly admixed

Another friend, who is a population genomicist himself, expressed some skepticism that such a long segment wasn’t broken up by recombination over the generations. My only moderately informed answer is this: we’d only notice the long segments, because if a very small region of ‘exotic’ ancestry was embedded within the dominant ancestral component it probably would not show up on some of these tests (or, we’d assume it was noise). Dan has another segment of South Asian ancestry, but much smaller in size. It may be there are other regions which we could find if we used better reference populations.

Here’s what I tentatively want to do with Dan’s data now. First, take the 80 MB or so which has South Asian ancestry, and phase it. That way I’d have a South Asian chromosome and a European one, and we could look for matches for only the South Asian one. But being busy I didn’t have time to do this. What I did have time to do was reduce the chromosomal region under consideration, and then run an IBS distance analysis in a private data set I have. This is a crude, but not always uninformative analysis. But by looking at the relationships I can now conclude that Dan MacArthur probably does not have Romani ancestry. Why? Because the Romani are of Northwest Indian heritage, and MacArthur’s match pattern using the diploid genotype (so South Asian + European) does not match what I expect would emerge from such a combination.

The full table is below, but to me the fact that he has so many matches with Northwest Indian populations is evidence that his ancestry was not Northwest Indian. Otherwise, he would be matching more Utah white (CEU samples) more often. Rather, someone with a mix of more conventional South Asian ancestry and European ancestry often resembles some of the less South Asian populations of South Asia (e.g., Brahui) in these crude measures. In fact, one of the closest matches to Dan’s IBS profile’s is that of my own mother. She is a rather vanilla ethnic Bengali, so I think there is a strong chance that his Indian ancestry issimilar. This weak genetic data isn’t really the primary reason. The British East India company operated out of Bengal for much of its history, and there are simply a lot of Bengalis.

There’s a lot more that can be done here. Since I don’t have time, here’s the pedigree file if anyone wants to play with them (Dan is DGM001).

Population

Genetic distance from Dan

Standardized distance

Brahui

0.253

81.268

Burusho

0.257

82.736

Razib’s Mother

0.258

82.783

CEU

0.258

82.993

Burusho

0.258

83.024

CEU

0.26

83.547

Sakilli

0.26

83.555

Brahui

0.261

83.831

Brahui

0.261

83.857

GIH

0.261

83.955

CEU

0.261

83.972

CEU

0.261

83.985

CEU

0.262

84.043

North Kannadi

0.262

84.169

CEU

0.262

84.207

CEU

0.262

84.318

CEU

0.262

84.33

CEU

0.263

84.391

Paniya

0.263

84.408

CEU

0.263

84.437

CEU

0.263

84.445

CEU

0.263

84.488

CEU

0.263

84.606

CEU

0.263

84.609

CEU

0.264

84.691

Brahui

0.264

84.709

CEU

0.264

84.752

CEU

0.264

84.764

Brahui

0.264

84.822

GIH

0.264

84.826

Burusho

0.264

84.841

CEU

0.264

84.898

CEU

0.264

84.975

North Kannadi

0.264

84.992

CEU

0.265

85.087

Paniya

0.265

85.212

CEU

0.265

85.226

CEU

0.265

85.25

CEU

0.265

85.25

CEU

0.265

85.278

CEU

0.265

85.299

North Kannadi

0.265

85.3

Burusho

0.265

85.309

Burusho

0.266

85.328

CEU

0.266

85.363

CEU

0.266

85.409

North Kannadi

0.266

85.412

CEU

0.266

85.436

Burusho

0.266

85.446

Bene Israel

0.266

85.508

CEU

0.266

85.521

GIH

0.266

85.618

GIH

0.267

85.661

CEU

0.267

85.696

CEU

0.267

85.722

CEU

0.267

85.732

Brahui

0.267

85.777

GIH

0.267

85.793

CEU

0.267

85.799

CEU

0.267

85.816

Cochin Jews

0.267

85.85

CEU

0.267

85.943

Brahui

0.268

85.996

CEU

0.268

86.005

Cochin Jews

0.268

86.011

CEU

0.268

86.08

CEU

0.268

86.115

CEU

0.268

86.18

GIH

0.268

86.229

Cochin Jews

0.268

86.234

CEU

0.268

86.244

Burusho

0.268

86.265

CEU

0.268

86.277

CEU

0.268

86.278

CEU

0.269

86.288

CEU

0.269

86.291

CEU

0.269

86.318

CEU

0.269

86.325

CEU

0.269

86.326

GIH

0.269

86.327

CEU

0.269

86.329

CEU

0.269

86.354

CEU

0.269

86.387

CEU

0.269

86.463

CEU

0.269

86.515

CEU

0.269

86.517

CEU

0.269

86.55

CEU

0.27

86.609

Paniya

0.27

86.682

CEU

0.27

86.687

CEU

0.27

86.696

CEU

0.27

86.717

CEU

0.27

86.733

Sakilli

0.27

86.74

CEU

0.27

86.866

Malayan

0.27

86.879

North Kannadi

0.27

86.883

CEU

0.271

86.937

Brahui

0.271

86.952

Burusho

0.271

86.956

CEU

0.271

86.957

CEU

0.271

86.977

North Kannadi

0.271

86.995

GIH

0.271

87.018

CEU

0.271

87.042

CEU

0.271

87.066

CEU

0.271

87.07

Brahui

0.271

87.09

Bene Israel

0.271

87.094

Sakilli

0.271

87.141

CEU

0.271

87.2

CEU

0.271

87.24

North Kannadi

0.272

87.253

CEU

0.272

87.297

Burusho

0.272

87.307

CEU

0.272

87.327

GIH

0.272

87.353

CEU

0.272

87.355

Cochin Jews

0.272

87.381

CEU

0.272

87.384

CEU

0.272

87.5

CEU

0.272

87.535

CEU

0.273

87.594

Malayan

0.273

87.676

CEU

0.273

87.702

CEU

0.273

87.741

Burusho

0.273

87.806

CEU

0.273

87.846

Cambodians

0.274

87.932

North Kannadi

0.274

87.951

CEU

0.274

87.951

Burusho

0.274

88.03

CEU

0.274

88.047

CEU

0.274

88.081

CEU

0.274

88.089

CEU

0.274

88.101

CEU

0.274

88.179

CEU

0.274

88.19

North Kannadi

0.275

88.243

CEU

0.275

88.32

GIH

0.275

88.325

CEU

0.275

88.349

Brahui

0.275

88.393

CEU

0.275

88.402

CEU

0.275

88.457

Bene Israel

0.276

88.552

CEU

0.276

88.577

CEU

0.276

88.603

CEU

0.276

88.647

CEU

0.276

88.7

CEU

0.276

88.729

CEU

0.276

88.814

CEU

0.276

88.85

Brahui

0.276

88.855

CEU

0.277

88.923

GIH

0.277

88.99

Paniya

0.277

89.082

CEU

0.277

89.118

CEU

0.277

89.15

CEU

0.277

89.151

CEU

0.277

89.17

CEU

0.278

89.184

Cambodians

0.278

89.208

Cambodians

0.278

89.233

Cambodians

0.278

89.383

CEU

0.278

89.45

CEU

0.278

89.493

Cambodians

0.279

89.522

CEU

0.279

89.595

CEU

0.279

89.679

CEU

0.279

89.753

CEU

0.279

89.762

CEU

0.279

89.807

Cambodians

0.28

89.942

GIH

0.28

90.085

CEU

0.281

90.178

Brahui

0.281

90.364

Cambodians

0.282

90.543

Cambodians

0.282

90.559

Cambodians

0.282

90.77

Cambodians

0.283

90.898

CEU

0.283

90.956

CEU

0.284

91.316

CHD

0.289

92.952

Sakilli

0.29

93.103

Bene Israel

0.29

93.122

CHD

0.291

93.619

CHD

0.291

93.663

CHD

0.293

94.125

CHD

0.293

94.248

CHD

0.294

94.451

CHD

0.294

94.629

CHD

0.296

94.965

CHD

0.296

95.279

Yorubas

0.297

95.298

CHD

0.297

95.368

CHD

0.297

95.438

CHD

0.297

95.441

Yorubas

0.297

95.567

CHD

0.298

95.678

CHD

0.298

95.828

CHD

0.299

96.032

CHD

0.299

96.127

CHD

0.3

96.349

CHD

0.3

96.403

CHD

0.3

96.443

CHD

0.3

96.508

CHD

0.3

96.523

CHD

0.3

96.533

CHD

0.301

96.575

CHD

0.301

96.598

CHD

0.301

96.624

CHD

0.301

96.625

CHD

0.301

96.738

CHD

0.301

96.758

CHD

0.301

96.869

Yorubas

0.302

97.106

CHD

0.303

97.37

CHD

0.303

97.41

Yorubas

0.304

97.681

CHD

0.304

97.713

CHD

0.304

97.747

Yorubas

0.304

97.829

CHD

0.304

97.838

CHD

0.305

98.106

CHD

0.306

98.309

Yorubas

0.307

98.499

CHD

0.307

98.546

CHD

0.307

98.547

CHD

0.307

98.606

CHD

0.307

98.764

CHD

0.307

98.78

CHD

0.307

98.803

Yorubas

0.308

98.947

Yorubas

0.308

99.03

Yorubas

0.309

99.411

Yorubas

0.309

99.417

CHD

0.309

99.452

CHD

0.31

99.624

Yorubas

0.311

100

Comments Off on A lighter shade of brown: the Dan MacArthur chronicles, not a Romani

A few days ago I suggested that Dr. Daniel MacArthur might have South Asian ancestry. Now, when confronted with surprise the best option is to stick with your prior assumption, unless that surprise is powerful enough for you to “update” your model. After a few days of further analysis I will update: I do think Dan MacArthur has South Asian ancestry. Dienekes dug further, and noticed that there are hallmarks of “Ancestral South Indian” ancestry along the first 2/3 or so of chromosome 10. Now, you do have to remember that this genomic region is only half South Asian. The other half is European.

But in any case, one question that some people brought up: perhaps MacArthur has Romani heritage? I’m skeptical of this partly because:

1) there weren’t that many Romani in Britain in the 19th century

2) The British Romani are already very highly admixed

Another friend, who is a population genomicist himself, expressed some skepticism that such a long segment wasn’t broken up by recombination over the generations. My only moderately informed answer is this: we’d only notice the long segments, because if a very small region of ‘exotic’ ancestry was embedded within the dominant ancestral component it probably would not show up on some of these tests (or, we’d assume it was noise). Dan has another segment of South Asian ancestry, but much smaller in size. It may be there are other regions which we could find if we used better reference populations.

Here’s what I tentatively want to do with Dan’s data now. First, take the 80 MB or so which has South Asian ancestry, and phase it. That way I’d have a South Asian chromosome and a European one, and we could look for matches for only the South Asian one. But being busy I didn’t have time to do this. What I did have time to do was reduce the chromosomal region under consideration, and then run an IBS distance analysis in a private data set I have. This is a crude, but not always uninformative analysis. But by looking at the relationships I can now conclude that Dan MacArthur probably does not have Romani ancestry. Why? Because the Romani are of Northwest Indian heritage, and MacArthur’s match pattern using the diploid genotype (so South Asian + European) does not match what I expect would emerge from such a combination.

The full table is below, but to me the fact that he has so many matches with Northwest Indian populations is evidence that his ancestry was not Northwest Indian. Otherwise, he would be matching more Utah white (CEU samples) more often. Rather, someone with a mix of more conventional South Asian ancestry and European ancestry often resembles some of the less South Asian populations of South Asia (e.g., Brahui) in these crude measures. In fact, one of the closest matches to Dan’s IBS profile’s is that of my own mother. She is a rather vanilla ethnic Bengali, so I think there is a strong chance that his Indian ancestry issimilar. This weak genetic data isn’t really the primary reason. The British East India company operated out of Bengal for much of its history, and there are simply a lot of Bengalis.

There’s a lot more that can be done here. Since I don’t have time, here’s the pedigree file if anyone wants to play with them (Dan is DGM001).

Population

Genetic distance from Dan

Standardized distance

Brahui

0.253

81.268

Burusho

0.257

82.736

Razib’s Mother

0.258

82.783

CEU

0.258

82.993

Burusho

0.258

83.024

CEU

0.26

83.547

Sakilli

0.26

83.555

Brahui

0.261

83.831

Brahui

0.261

83.857

GIH

0.261

83.955

CEU

0.261

83.972

CEU

0.261

83.985

CEU

0.262

84.043

North Kannadi

0.262

84.169

CEU

0.262

84.207

CEU

0.262

84.318

CEU

0.262

84.33

CEU

0.263

84.391

Paniya

0.263

84.408

CEU

0.263

84.437

CEU

0.263

84.445

CEU

0.263

84.488

CEU

0.263

84.606

CEU

0.263

84.609

CEU

0.264

84.691

Brahui

0.264

84.709

CEU

0.264

84.752

CEU

0.264

84.764

Brahui

0.264

84.822

GIH

0.264

84.826

Burusho

0.264

84.841

CEU

0.264

84.898

CEU

0.264

84.975

North Kannadi

0.264

84.992

CEU

0.265

85.087

Paniya

0.265

85.212

CEU

0.265

85.226

CEU

0.265

85.25

CEU

0.265

85.25

CEU

0.265

85.278

CEU

0.265

85.299

North Kannadi

0.265

85.3

Burusho

0.265

85.309

Burusho

0.266

85.328

CEU

0.266

85.363

CEU

0.266

85.409

North Kannadi

0.266

85.412

CEU

0.266

85.436

Burusho

0.266

85.446

Bene Israel

0.266

85.508

CEU

0.266

85.521

GIH

0.266

85.618

GIH

0.267

85.661

CEU

0.267

85.696

CEU

0.267

85.722

CEU

0.267

85.732

Brahui

0.267

85.777

GIH

0.267

85.793

CEU

0.267

85.799

CEU

0.267

85.816

Cochin Jews

0.267

85.85

CEU

0.267

85.943

Brahui

0.268

85.996

CEU

0.268

86.005

Cochin Jews

0.268

86.011

CEU

0.268

86.08

CEU

0.268

86.115

CEU

0.268

86.18

GIH

0.268

86.229

Cochin Jews

0.268

86.234

CEU

0.268

86.244

Burusho

0.268

86.265

CEU

0.268

86.277

CEU

0.268

86.278

CEU

0.269

86.288

CEU

0.269

86.291

CEU

0.269

86.318

CEU

0.269

86.325

CEU

0.269

86.326

GIH

0.269

86.327

CEU

0.269

86.329

CEU

0.269

86.354

CEU

0.269

86.387

CEU

0.269

86.463

CEU

0.269

86.515

CEU

0.269

86.517

CEU

0.269

86.55

CEU

0.27

86.609

Paniya

0.27

86.682

CEU

0.27

86.687

CEU

0.27

86.696

CEU

0.27

86.717

CEU

0.27

86.733

Sakilli

0.27

86.74

CEU

0.27

86.866

Malayan

0.27

86.879

North Kannadi

0.27

86.883

CEU

0.271

86.937

Brahui

0.271

86.952

Burusho

0.271

86.956

CEU

0.271

86.957

CEU

0.271

86.977

North Kannadi

0.271

86.995

GIH

0.271

87.018

CEU

0.271

87.042

CEU

0.271

87.066

CEU

0.271

87.07

Brahui

0.271

87.09

Bene Israel

0.271

87.094

Sakilli

0.271

87.141

CEU

0.271

87.2

CEU

0.271

87.24

North Kannadi

0.272

87.253

CEU

0.272

87.297

Burusho

0.272

87.307

CEU

0.272

87.327

GIH

0.272

87.353

CEU

0.272

87.355

Cochin Jews

0.272

87.381

CEU

0.272

87.384

CEU

0.272

87.5

CEU

0.272

87.535

CEU

0.273

87.594

Malayan

0.273

87.676

CEU

0.273

87.702

CEU

0.273

87.741

Burusho

0.273

87.806

CEU

0.273

87.846

Cambodians

0.274

87.932

North Kannadi

0.274

87.951

CEU

0.274

87.951

Burusho

0.274

88.03

CEU

0.274

88.047

CEU

0.274

88.081

CEU

0.274

88.089

CEU

0.274

88.101

CEU

0.274

88.179

CEU

0.274

88.19

North Kannadi

0.275

88.243

CEU

0.275

88.32

GIH

0.275

88.325

CEU

0.275

88.349

Brahui

0.275

88.393

CEU

0.275

88.402

CEU

0.275

88.457

Bene Israel

0.276

88.552

CEU

0.276

88.577

CEU

0.276

88.603

CEU

0.276

88.647

CEU

0.276

88.7

CEU

0.276

88.729

CEU

0.276

88.814

CEU

0.276

88.85

Brahui

0.276

88.855

CEU

0.277

88.923

GIH

0.277

88.99

Paniya

0.277

89.082

CEU

0.277

89.118

CEU

0.277

89.15

CEU

0.277

89.151

CEU

0.277

89.17

CEU

0.278

89.184

Cambodians

0.278

89.208

Cambodians

0.278

89.233

Cambodians

0.278

89.383

CEU

0.278

89.45

CEU

0.278

89.493

Cambodians

0.279

89.522

CEU

0.279

89.595

CEU

0.279

89.679

CEU

0.279

89.753

CEU

0.279

89.762

CEU

0.279

89.807

Cambodians

0.28

89.942

GIH

0.28

90.085

CEU

0.281

90.178

Brahui

0.281

90.364

Cambodians

0.282

90.543

Cambodians

0.282

90.559

Cambodians

0.282

90.77

Cambodians

0.283

90.898

CEU

0.283

90.956

CEU

0.284

91.316

CHD

0.289

92.952

Sakilli

0.29

93.103

Bene Israel

0.29

93.122

CHD

0.291

93.619

CHD

0.291

93.663

CHD

0.293

94.125

CHD

0.293

94.248

CHD

0.294

94.451

CHD

0.294

94.629

CHD

0.296

94.965

CHD

0.296

95.279

Yorubas

0.297

95.298

CHD

0.297

95.368

CHD

0.297

95.438

CHD

0.297

95.441

Yorubas

0.297

95.567

CHD

0.298

95.678

CHD

0.298

95.828

CHD

0.299

96.032

CHD

0.299

96.127

CHD

0.3

96.349

CHD

0.3

96.403

CHD

0.3

96.443

CHD

0.3

96.508

CHD

0.3

96.523

CHD

0.3

96.533

CHD

0.301

96.575

CHD

0.301

96.598

CHD

0.301

96.624

CHD

0.301

96.625

CHD

0.301

96.738

CHD

0.301

96.758

CHD

0.301

96.869

Yorubas

0.302

97.106

CHD

0.303

97.37

CHD

0.303

97.41

Yorubas

0.304

97.681

CHD

0.304

97.713

CHD

0.304

97.747

Yorubas

0.304

97.829

CHD

0.304

97.838

CHD

0.305

98.106

CHD

0.306

98.309

Yorubas

0.307

98.499

CHD

0.307

98.546

CHD

0.307

98.547

CHD

0.307

98.606

CHD

0.307

98.764

CHD

0.307

98.78

CHD

0.307

98.803

Yorubas

0.308

98.947

Yorubas

0.308

99.03

Yorubas

0.309

99.411

Yorubas

0.309

99.417

CHD

0.309

99.452

CHD

0.31

99.624

Yorubas

0.311

100

Comments Off on A lighter shade of brown: the Dan MacArthur chronicles, not a Romani

December 10, 2012

My initial inclination in this post was to discuss a recent ordering snafu which resulted in many of my friends being quite peeved at 23andMe. But browsing through their new ‘ancestry composition’ feature I thought I had to discuss it first, because of some nerd-level intrigue. Though I agree with many of Dienekes concerns about this new feature, I have to admit that at least this method doesn’t give out positively misleading results. For example, I had complained earlier that ‘ancestry painting’ gave literally crazy results when they weren’t trivial. It said I was ~60 percent European, which makes some coherent sense in their non-optimal reference population set, but then stated that my daughter was >90 percent European. Since 23andMe did confirm she was 50% identical by descent with me these results didn’t make sense; some readers suggested that there was a strong bias in their algorithms to assign ambiguous genomic segments to ‘European’ heritage (this was a problem for East Africans too).

Here’s my daughter’s new chromosome painting:

One aspect of 23andMe’s new ancestry composition feature is that it is very Eurocentric. But, most of the customers are white, and presumably the reference populations they used (which are from customers) are also white. Though there are plenty of public domain non-white data sets they could have used, I assume they’d prefer to eat their own data dog-food in this case. But that’s really a minor gripe in the grand scheme of things. This is a huge upgrade from what came before. Now, it’s not telling me, as a South Asian, very much. But, it’s not telling me ludicrous things anymore either!

But in regards to omission I am curious to know why this new feature rates my family as only ~3% East Asian, when other analyses put us in the 10-15% range. The problem with very high values is that South Asians often have some residual ‘eastern’ signal, which I suspect is not real admixture, but is an artifact. Nevertheless, northeast Indians, including Bengalis, often have genuine East Asia admixture. On PCA plots my family is shifted considerably toward East Asians. The signal they are picking up probably isn’t noise. Almost every apportionment of East Asian ancestry I’ve seen for my family yields a greater value for my mother, and that holds here. It’s just that the values are implausibly low.

In any case, that’s not the strangest thing I saw. I was clicking around people who I had “shared” genomes with, and I stumbled upon this:

As you can guess from the screenshot this is Daniel MacArthur’s profile. And according to this ~25% of chromosome 10 is South Asian! On first blush this seemed totally nonsensical to me, so I clicked around other profiles of people of similar Northern European background…and I didn’t see anything equivalent.

What to do? It’s going to take more evidence than this to shake my prior assumptions, so I downloaded Dr. MacArthur’s genotype. Then I merged it with three HapMap populations, the Utah whites (CEU), the Gujaratis (GIH), and the Chinese from Denver (CHD). The last was basically a control. I pulled out chromosome 10. I also added Dan’s wife Ilana to the data set, since I believe she got typed with the same Illumina chip, and is of similar ethnic background (i.e., very white). It is important to note that only 28,000 SNPs remained in the data set. But usually 10,000 is more than sufficient on SNP data for model-based clustering with inter-continental scale variation.

I did two things:

1) I ran ADMIXTURE at K = 3, unsupervised

2) I ran an MDS, which visualized the genetic variation in multiple dimensions

Before I go on, I will state what I found: these methods supported the inference from 23andMe, on chromosome 10 Dr. MacArthur seems to have an affinity with South Asians (i.e., this is his ‘curry chromosome’). Here are the average (median) values in tabular format, with MacArthur and his wife presented for comparison.

ADMIXTURE results for chromosome 10

K 1

K 2

K 3

CEU

0.04

0.02

0.93

GIH

0.87

0.05

0.08

CHD

0.01

0.97

0.01

Daniel MacArthur

0.29

0.07

0.64

Ilana Fisher

0.01

0.06

0.94

You probably want a distribution. Out of the non-founder CEU sample none went above 20% South Asian. Though it did surprise me that a few were that high, making it more plausible to me that MacArthur’s results on chromosome 10 were a fluke:

And here’s the MDS with the two largest dimensions:

Again, it’s evident that this chromosome 10 is shifted toward South Asians. If I had more time right now what I’d do is probably get that specific chromosomal segment, phase it, and then compare it to various South Asian populations. But I don’t have time now, so I went and checked out the results from the Interpretome. I cranked up the settings to reduce the noise, and so that it would only spit out the most robust and significant results. As you can see, again chromosome 10 comes up as the one which isn’t quite like the others.

Is there is a plausible explanation for this? Perhaps Dr. MacArthur can call up a helpful relative? From what recall his parents are immigrants from the United Kingdom, and it isn’t unheard of that white Britons do have South Asian ancestry which dates back to the 19th century. Though to be totally honest I’m rather agnostic about all this right now. This genotype has been “out” for years now, so how is it that no one has noticed this peculiarity??? Perhaps the issue is that everyone was looking at the genome wide average, and it just doesn’t rise to the level of notice? What I really want to do is look at the distribution of all chromosomes and see how Daniel MacArthur’s chromosome 10 then stacks up. It might be a random act of nature yet.

Also, I guess I should add that at ~1.5% South Asian that would be consistent with one of MacArthur’s great-great-great-great grandparents being Indian. Assuming 25 year generation times that puts them in the mid-19th century. Of course, at such a low proportion the variance is going to be high, so it is quite possible that you need to push the real date of admixture one generation back, or one generation forward.